The first aim of this investigation is to establish a model to study the regulation of intraocular pressure (IOP) by the central nervous system (CNS) by using ventriculocisternal perfusion. Adult New Zealand pigmented rabbits will undergo surgical insertion of two lateral guide tubes and one cisternal guide tube. Two weeks after surgery, the conscious rabbits will be perfused with various buffered, sterile osmotic solutions at 37 degrees C. The response and time course of alteration of IOP will be followed for each perfusate. The second aim of this investigation is to study whether intracranially and topically administered Beta-adrenergic antagonist, timolol, affect this CNS-IOP model. Intracranial perfusion of artificial cerebrospinal fluid with various concentrations of timolol will be performed in those rabbits which are responsive to perfusion of osmotic solutions. Changes in IOP and dose-response curves for this action will be recorded. The mechanism by which centrally perfused osmotic solutions alter IOP will be studied by pretreating these rabbits with topical timolol and testing the blocking activity on the alteration of IOP. The third aim of this investigation is to study how superior cervical ganglionectomy affects this model and the action of timolol on this model. Experiments described above will be carried out in rabbits with unilateral superior cervical ganglionectomy. The analysis of data from denervated eyes will indicate whether adrenergic nerves are involved in the CNS regulation of IOP. Information obtained from this investigation will clarify not only the nature of CNS regulation of IOP, but also the existence of a CNS locus of action for timolol. This work may eventually lead to a broader rationale for the development of new type of antiglaucoma drugs acting through the CNS.